自然殺手細胞經NKG2D/NCR訊息傳遞路徑直接毒殺Mycobacterium kansasii

Direct killing of Mycobacterium kansasii by NK cells via NKG2D / NCR-dependent signaling pathway

張明雯(Ming-Wen Chang)

指導教授 ： 宋瑞珍

國立中央大學/理學院/生命科學系/碩士(2011年)

摘要

自然殺手細胞在宿主先天免疫防禦系統中，扮演了很重要的角色。目前已知其主要的功能為殺死腫瘤細胞或被病毒感染的宿主細胞。然而，自然殺手細胞是否能直接殺死微生物仍然所知甚少。以往的研究顯示，自然殺手細胞可以使用細胞毒性蛋白，例如穿孔素和顆粒溶素直接殺死新型隱球菌-一個致病的酵母菌。因為堪薩斯分枝桿菌所造成的慢性肺部感染與結核分枝桿菌所造成的肺結核相似，本研究中，利用此菌作為研究對象，我探討並發現人類自然殺手細胞株，NK92細胞具有殺死致病細菌-堪薩斯分枝桿菌之現象。進一步研究其毒殺的機制得知，此致死作用是藉由NK92細胞與堪薩斯分枝桿菌的直接接觸所造成。穿孔素和顆粒溶素在其中扮演重要角色，且其中作用的機制是通過活化NKG2D/NCRs, ERK，JNK及p38 MAPK的訊息傳遞路徑所進行。

關鍵字

訊息傳遞路徑 ； 堪薩斯分枝桿菌 ； 自然殺手細胞

並列摘要

Natural killer (NK) cells play a pivotal role in the effector arm of host innate immunity defense system. The major functions of NK cells in killing tumor cells or virus-infected host cells were well established. However, whether NK cells can directly kill microbes remains poorly understood. Previous studies have shown that NK cells can use the cytolytic proteins, perforin and granulysin to directly kill the yeast pathogen Cryptococcus neoformans. In this study, using the pathogenic mycobacterium Mycobacterium kansasii which causes a chronic pulmonary infection resembling pulmonary tuberculosis as the study model, I showed that human NK-92 cells directly kill mycobacterium. Killing of M. kansasii by NK92 cells is contact dependent. NK cells use the cytolytic proteins, perforin and granulysin for direct killing, and the underlying killing mechanism is through NKG2D/NCRs, ERK, JNK and p38 MAPK signaling pathways.

並列關鍵字

signaling pathway ； Mycobacterium kansasii ； Natural killer cells

參考文獻

3. Ting-Shu Wu 2, Chia-Chen Lu 1 and Hsin-Chih Lai 1. 2009. Current Situations on Identification of Nontuberculous Mycobacteria J Biomed Lab Sci 21:6.

1. Jarzembowski, J. A., and M. B. Young. 2008. Nontuberculous mycobacterial infections. Arch Pathol Lab Med 132:1333-1341.

2. Guerardel, Y., E. Maes, V. Briken, F. Chirat, Y. Leroy, C. Locht, G. Strecker, and L. Kremer. 2003. Lipomannan and lipoarabinomannan from a clinical isolate of Mycobacterium kansasii: novel structural features and apoptosis-inducing properties. J Biol Chem 278:36637-36651.

4. Ellis, S. M. 2004. The spectrum of tuberculosis and non-tuberculous mycobacterial infection. Eur Radiol 14 Suppl 3:E34-42.

5. Razavi, B., and M. G. Cleveland. 2000. Cutaneous infection due to Mycobacterium kansasii. Diagn Microbiol Infect Dis 38:173-175.